Severe trauma to peripheral nerves often results in long-term disability and loss of personal autonomy. The number of persons suffering from nerve injuries is approximately 1 million per year. Enhancing recovery from such injuries would obviously be of utmost benefit. One of the few techniques that can be applied easily and non-invasively to accelerate the healing process involves the use of pulsed electromagnetic fields (PEMF). In our laboratory we have observed a statistically significant 22% increase in the rate of regeneration when PEMF is applied after crush lesion of rat sciatic nerve. This enhancement is comparable to that achieved by drugs, growth factors or surgical "conditioning lesions." If applied to the animal before the nerve injury, we also observed a heightened regenerative response. Our objective in these studies is to determine the mechanisms underlying the promotion of increased nerve regeneration by PEMF in an animal model. The mechanisms to be addressed are: (1) modification of slow axonal transport, (2) upregulation of RNA and protein synthesis in neuronal cells for the regrowth of nerve fibers, (3) augmentation of synthesis of mitogens and trophic factors from cells at the site of injury and in the distal segment, and (4) interaction with exogenous nerve growth factor to promote cell survival. Lastly, we will address these mechanistic questions on parallel cell culture models treated with the electromagnetic fields.